Toshiki Okasaka

hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type.

Human 8-oxoguanine DNA glycosylase 1 (hOGG1) has a major role in the repair of 8-hydroxyguanine, a major promutagenic DNA lesion. The genetic polymorphism rs1052133, which leads to substitution of the amino acid at codon 326 from Ser to Cys, shows functional differences, namely a decrease in enzyme activity in hOGG1-Cys326. Although several studies have investigated the association between rs1052133 and lung cancer susceptibility, the effect of this locus on lung cancer according to histology remains unclear. We therefore conducted a case–control study with 515 incident lung cancer cases and 1030 age- and sex-matched controls without cancer, and further conducted a meta-analysis. In overall analysis, the homozygous Cys/Cys genotype showed a significant association with lung cancer compared to Ser allele carrier status (odds ratio (OR)=1.31, 95% confidence interval (CI)=1.02–1.69). By histology-based analysis, the Cys/Cys genotype showed a significantly positive association with small-cell carcinoma (OR=2.40, 95% CI=1.32–4.49) and marginally significant association with adenocarcinoma (OR=1.32, 95% CI=0.98–1.77). A meta-analysis of previous and our present study revealed that this polymorphism is positively associated with adenocarcinoma, although suggestive associations were also found for squamous- and small-cell lung cancers. These results indicate that rs1052133 contributes to the risk of adenocarcinoma of lung.

Can non-performance of radical systematic mediastinal lymphadenectomy be justified in elderly lung cancer patients? An evaluation using propensity-based survival analysis

OBJECTIVES The increasing age of the population has raised the importance of determining the minimally required surgical treatment for elderly lung cancer patients. Despite a number of previous studies, the therapeutic impact of a radical mediastinal lymphadenectomy (RLA) associated with a pulmonary resection for lung cancer remains controversial. Herein, we investigated the impact of lymph node dissection on the overall survival for elderly lung cancer patients and assessed whether the non-performance of an RLA could be justified in the surgical treatment for these elderly patients. METHODS We analysed the data for 160 patients aged 70 years and older (113 males, 47 females) who underwent curative-intent surgery for non-small-cell lung cancer. They were divided into two groups, according to the method used for the intra-operative mediastinal lymph node dissection, the radical systematic lymphadenectomy (RLA, n=76) and the non-radical lymphadenectomy (NLA, n=94) groups. A Cox proportional hazards model and the Kaplan-Meier method were used for the survival analyses. Propensity-based analyses were also used to reduce the effect of non-randomisation and possible bias in indication of treatment between the two groups. RESULTS RLAs had no protective effect on mortality; the hazard ratio for the RLA group in comparison to the NLA group was 0.97 (95% confidence interval (CI): 0.32-2.89) in the multivariate analysis and 1.43 (95% CI: 0.42-4.91) in the propensity-based stratifying analysis. The 3-year survival probability was 81.3% (95% CI: 67.1-89.8) for the NLA group, which was marginally better than that of the RLA group (77.5% (95% CI: 63.3-86.8)). There was no significant difference in the overall survival between the two groups (p=0.26). The 3-year survival probability of the NLA group at each quartile of the propensity score also tended to be better than that of the RLA group, which did not show any significant difference. CONCLUSIONS There was no survival benefit shown for RLA associated with pulmonary resections in the present cohort, even in the propensity-based analyses. Although some reports recommend a systematic mediastinal lymphadenectomy for proper staging and better survival, a pulmonary resection with non-performance of radical lymphadenectomy could be an acceptable surgical treatment for the increasing number of elderly lung cancer patients.

Stepwise examination for differential diagnosis of primary lung cancer and breast cancer relapse presenting as a solitary pulmonary nodule in patients after mastectomy

The distinction of primary lung from metastatic breast cancer is crucial in patients presenting with a solitary pulmonary nodule after mastectomy, because treatment strategies are completely different. Definitive diagnosis of these nodules, however, is often difficult. We assessed the feasibility of our diagnostic approach for these nodules and estimated the frequency of primary lung cancer occurrence in patients after mastectomy.

Alterations in Renal Uptake Kinetics of the Xanthine Derivative Enprofylline in Endotoxaemic Mice

The pharmacokinetics and renal uptake of enprofylline, which is primarily excreted into the urine by an active tubular secretion mechanism, were investigated in endotoxaemic mice by lipopolysaccharide isolated from Klebsiella pneumoniae.

Clinical evaluation of a new tumour–node–metastasis staging system for thymic malignancies proposed by the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and the International Thymic Malignancy Interest Group

OBJECTIVES The tumour-node-metastasis classification has been widely used as a guide for estimating prognosis, and is the basis for treatment decisions in patients with malignant tumours. The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and the International Thymic Malignancy Interest Group have proposed a new staging system for thymic malignancies. However, its validity has not been fully established. In this study, we assessed the systems utilities and drawbacks. METHODS We reviewed 154 consecutive patients with thymic epithelial tumours who underwent complete resection at our institution, and compared their characteristics and outcomes when classified according to the proposed system with those when classified under the Masaoka-Koga system. RESULTS The proportion of patients with Stage I disease increased remarkably to 77.3% when using the proposed system because of the reclassification of Masaoka-Koga stages II and III diseases. Among 69 patients with Type A, AB or B1 thymoma, 68 tumours (98%) were reclassified as Stage I disease. Moreover, the proportion of Stage III and IV tumours increased in concordance with Types B2, B3 thymomas and thymic carcinoma. Under the proposed new system, the recurrence-free survival rates showed significant deterioration with increasing stage, while the overall survival curves did not. CONCLUSIONS The newly proposed classification for thymic malignancies does not serve as a prognostic prediction model for overall survival but served as a significant imbalance of stage distribution in our cohort. However, it appears to be beneficial, especially in clinical settings and recurrence-free survival analysis.

Late breast metastasis from resected lung cancer diagnosed by epidermal growth factor receptor gene mutation

Primary lung cancer metastasizes to various organs, but rarely metastasizes to the breast. We report a case of breast metastasis from primary lung cancer, which was confirmed by the detection of the same epidermal growth factor receptor (EGFR) gene mutation.

Complete Spontaneous Regression of Non-small Cell Lung Cancer Followed by Adrenal Relapse

Spontaneous regression (SR) of cancer is a rare phenomenon. SR is recognized as complete or partial disappearance of the disease after inadequate or no treatment. Although reports of this phenomenon have been documented for several malignancies, it is rare in patients with lung cancer. In most documented cases, diagnoses of SR were made based on only the radiologic findings. We herein report a case of complete SR of non-small cell lung cancer (NSCLC) that was pathologically proven using a resected specimen. Moreover, despite the local complete SR, the patient subsequently experienced an adrenal metastasis after surgery. To the best of our knowledge, this is the first report of a patient with NSCLC in whom complete regression of the primary site was observed, but in whom a distant metastasis became apparent. Both phenomena were pathologically proven. Our report suggests that both SR and tumor progression can proceed simultaneously.

Marginal pulmonary function is associated with poor short- and long-term outcomes in lung cancer surgery

ABSTRACT We sought to determine the short- and long-term prognoses among ‘marginal-risk’ non-small cell lung cancer patients who have a predicted postoperative- (ppo) forced expiratory volume in the first second (FEV1) of 30–60% and/or a ppo-diffusing capacity of the lung for carbon monoxide (DLCO) of 30–60%. The present study included 73 ‘marginal-risk’ and 318 ‘normal-risk’ patients who underwent anatomical resection for clinical stage I lung cancer between 2008 and 2012. The rates of postoperative morbidity, prolonged hospital stay, and overall survival were assessed. Postoperative morbidity occurred in 35 (48%) ‘marginal-risk’ patients and 66 (21%) ‘normal-risk’ patients, and 17 (23%) ‘marginal-risk’ patients and 20 (6%) ‘normal-risk’ patients required a prolonged hospital stay. The three- and five-year survival rates were 79% and 64% in the ‘marginal-risk’ patients and 93% and 87% in the ‘normal-risk’ patients, respectively. A ‘marginal-risk’ status was a significant factor in the prediction of postoperative morbidity (odds ratio [OR] 2.97, p < 0.001), the rate of prolonged hospital stay (OR 3.83, p < 0.001), and overall survival (hazard ratio 2.07, p = 0.028). In conclusion, ‘Marginal-risk’ patients, who are assessed based on ppo-values, comprise a subgroup of patients with poorer short- and long-term postoperative outcomes.

Multiple Thymic Carcinoids

We present a very rare case of simultaneous thymic carcinoids with similar size, one of which showed spontaneous regression. A 68-year-old man was admitted to the hospital because of two similar abnormal masses at his anterior mediastinum on chest computed tomography, one of which had decreased from 25 to 16 mm in diameter. A total thymectomy was performed and the pathologic examinations revealed that both tumors were atypical carcinoids. There have been seldom reports of multiple thymic carcinoids, and this case might suggest that total thymectomy is the best way to treat thymic carcinoid because of the possibility of multicentric origins.

The diffusing capacity of the lung for carbon monoxide is associated with the histopathological aggressiveness of lung adenocarcinoma

OBJECTIVES The diffusing capacity of the lung for carbon monoxide (DLCO) is an indicator of lung damage. We sought to determine whether DLCO is associated with the aggressiveness of lung adenocarcinoma using histopathological indexes, such as tumour differentiation, scar grade, nuclear atypia and the mitotic index. METHODS Fifty-seven patients with low DLCO (≤80% of predicted) and 466 patients with normal DLCO (>80% of predicted) who underwent R0 resection of lung adenocarcinoma between 2005 and 2012 were retrospectively reviewed. The relationships between the DLCO status and each histopathological index as well as the overall survival were evaluated. RESULTS Low DLCO had significant relationships with moderate/poor differentiation (79% vs 57% [low DLCO vs normal DLCO]), scar grade 3/4 (37% vs 18%), nuclear atypia 3 (65% vs 30%) and the mitotic index 3 (26% vs 8%). After adjusting for the age, sex, forced expiratory volume in 1 s, smoking status and tumour size, a low DLCO still showed a significant correlation with the histopathological indexes. These histopathological indexes were all significant factors for the overall survival on log-rank tests. In a multivariable Cox regression analysis with 13 clinicopathological variables, moderate/poor differentiation and nuclear atypia Grade 3 were significant histopathological factors for the overall survival (hazard ratios: 2.16 and 1.84; 95% confidence intervals: 1.10-4.51 and 1.06-3.21; P = 0.024 and 0.029, respectively). CONCLUSIONS Our findings regarding the relationship between DLCO and the histopathological indexes of lung adenocarcinoma suggest that lung damage may be associated with carcinogenesis and progression.